HIV Self-testing Among Previously Diagnosed HIV-Positive People in Khayelitsha, South Africa: No Evidence of Harm but may Facilitate Re-engagement in ART Care.

In South Africa, where an estimated 34% of nearly 7-million HIV-positive people were not on antiretroviral therapy (ART) in 2019, innovative strategies to diagnose and link people to care are needed. HIV self-testing (HIVST) is one such strategy. However, there is concern that access to HIVST might result in re-testing among people on ART, with a risk of false negative results and disengagement from care. Between November 2017 and December 2018, HIVST kits were distributed at a private pharmacy and at HIV testing outreach events. Each participant was instructed to report their result via SMS and those who did not were followed-up telephonically 10 days later. Electronic medical records of participants were searched for evidence of HIV services 6 months before and after enrollment. Of 1482 participants, 163 (11%) were previously diagnosed HIV-positive prior to taking the test. Of these, 123 reported a result, however 87% reported a negative result. Of the 163 previously diagnosed, 84 were not in ART care prior to the test, with 15 (18%) linking to care post-test. Of 79 who were in ART care prior to the test, 76 (96%) remained in care, even though 51 (67%) had reported a negative result. Overall, 29% of participants reported their result via SMS, and 48% when telephoned. Despite efforts to dissuade them, some previously diagnosed HIV-positive utilised HIVST. For those disengaged from care this may facilitate re-engagement. Self-testing among those already in care, regardless of the reported result, did not disrupt their treatment, and their reasons for doing the test remain unclear.

Delivering PrEP to Young Women in a Low-Income Setting in South Africa: Lessons for Providing Both Convenience and Support.

Daily oral pre-exposure prophylaxis (PrEP) is a key tool in addressing high HIV incidence among young women, and breaking the cycle of transmission. From 2017 to 2020, Médecins Sans Frontières (MSF) offered PrEP, in conjunction with contraception and risk-reduction counselling, to women aged 18-25, in a government-run clinic in Khayelitsha, a low income high HIV prevalence area in South Africa. Drawing on clinical, quantitative, and qualitative interview data, we describe participants' experiences and engagement with the PrEP program, participant adherence (measured by TFV-DP levels in dried blood spots) over time, and the indirect benefits of the PrEP program. Of 224 screened and eligible participants, 164 (73.2%) initiated PrEP, with no large differences between those who initiated and those who did not. Overall, 47 (29%) completed 18 months follow-up, with 15 (9.1%) attending all visits. 76 (46.9%) participants were lost to follow-up, 15 (9.1%) exited when leaving the area, and 28.7% of exits happened in the first month of the study. We identified two different trajectories of PrEP adherence: 67% of participants had, on average, consistently low TFV-DP levels, with the remaining 33% having sustained high adherence. Few baseline characteristics predicted good adherence. The main reported barrier to taking PrEP was forgetting to take or travel with the pills. Encouragement from others declined as a reported facilitator from month 6 to 18 (family: 93.1% vs 77.6%, p = 0.016, friends: 77.6% vs 41.4%, p ≤ 0.001, partners: 62.1% vs 46.6%, p = 0.096, other PrEP users: 89.7% vs 74.1%, p = 0.020). Disclosure to friends and family in some cases opened dialogue around sex, and helped to educate others about PrEP. Self-reported sex with more than one partner, and sex without a condom, decreased significantly after enrolment (p < 0.001, p = 0.063). In the individual interviews, participants credited their PrEP experience with changing their behaviour. Recognising the challenges with, but overall benefits from a package of care that includes the option of PrEP, lessons drawn from this study can help maximise persistence on PrEP within resource constraints. PrEP providers need to address participants' need for both convenience and social support.

A cluster randomized controlled trial of extending ART refill intervals to six-monthly for anti-retroviral adherence clubs.

BACKGROUND: The antiretroviral therapy (ART) adherence club (AC) differentiated service delivery model, where clinically stable ART patients receive their ART refills and psychosocial support in groups has supported clinically stable patients' retention and viral suppression. Patients and health systems could benefit further by reducing visit frequency and increasing ART refills. We designed a cluster-randomized control trial comparing standard of care (SoC) ACs and six-month ART refill (Intervention) ACs in a large primary care facility in Khayelitsha, South Africa. METHODS: Existing ACs were randomized to either the control (SOC ACs) or intervention (Intervention ACs) arm. SoC ACs meet five times annually, receiving two-month ART refills with a four-month ART refill over year-end. Blood is drawn at the AC visit ahead of the clinical assessment visit. Intervention ACs meet twice annually receiving six-month ART refills, with a third individual visit for routine blood collection anytime two-four weeks before the annual clinical assessment AC visit. Primary outcomes will be retention in care, annual viral load assessment completion and viral load suppression. (<400copies/mL) after 2 years. Ethics approval has been granted by the University of Cape Town (HREC 652/2016) and the Medecins Sans Frontieres (MSF) Ethics Review Board (#1639). Results will be published in peer-reviewed journals and made widely available through presentations and briefing documents. DISCUSSION: Evaluation of an extended ART refill interval in adherence clubs will provide evidence towards novel model adaptions that can be made to further improve convenience for patients and leverage health system efficiencies. TRIAL REGISTRATION: Registered with the Pan African Clinical Trial Registry: PACTR201810631281009. Registered 11 September 2018.

The epidemiology of rape and sexual violence in the platinum mining district of Rustenburg, South Africa: Prevalence, and factors associated with sexual violence.

BACKGROUND: Estimates for the prevalence of rape and other forms of sexual violence (SV) vary in South Africa. This survey aimed to provide clarity by quantifying the prevalence of SV (forced sex or sexual acts) by 1) sexual partners, and 2) non-partners, and to describe factors associated with these outcomes among women (18-49 years) living in Rustenburg Municipality. MATERIALS AND METHODS: We conducted a cluster-randomized household survey (November-December 2015). Women were asked about their experiences of SV, associated attitudes and behaviours, and access to services. Logistic regression was used to determine factors associated with partner and non-partner SV. RESULTS: Of eligible households, 83·1% (1700/2044) participated. Of 966 women invited, 836 participated (86·5%). Average age of participants was 31.6 years (95%CI: 30·9, 32·4) with 45% having completed at least secondary school, and 60% unemployed or looking for work. Lifetime prevalence of SV was 24.9% (95%CI: 21·7-28·5), reaching 9.0% (95% CI: 6·6-12·1) by age 15. Almost one third told no one of their SV experiences. Factors related to financial dependence were associated with SV by a partner. History of termination of pregnancy increased the likelihood of SV by a non-partner as an adult. Women who experienced SV in childhood or as an adult were more likely to experience SV from a different type of perpetrator than those who did not. CONCLUSIONS: We found a high prevalence of SV, including during childhood, in this setting, with limited access to care. This and the high morbidity attributed to SV calls for increased service provision.

Investigating the addition of oral HIV self-tests among populations with high testing coverage - Do they add value? Lessons from a study in Khayelitsha, South Africa.

INTRODUCTION: HIV self-testing (HIVST) offers a useful addition to HIV testing services and enables individuals to test privately. Despite recommendations to the contrary, repeat HIV testing is frequent among people already on anti-retroviral treatment (ART) and there are concerns that oral self-testing might lead to false negative results. A study was conducted in Khayelitsha, South Africa, to assess feasibility and uptake of HIVST and linkage-to-care following HIVST. METHODS: Participants were recruited at two health facilities from 1 March 2016 to 31 March 2017. People under 18 years, or with self-reported previously-diagnosed HIV infection, were excluded. Participants received an OraQuick Rapid HIV-1/2 Antibody kit, and reported their HIVST results by pre-paid text message (SMS) or by returning to the facility. Those not reporting within 7 days were contacted by phone. Electronic and paper-based clinical and laboratory records were retrospectively examined for all participants to identify known HIV outcomes, after matching for name, date of birth, and sex. These findings were compared with self-reported HIVST results where available. RESULTS: Of 639 participants, 401 (62.8%) self-reported a negative HIVST result, 27 (4.2%) a positive result, and 211 (33.0%) did not report. The record search identified that of the 401 participants self-reporting a negative HIVST result, 19 (4.7%) were already known to be HIV positive; of the 27 self-reporting positive, 12 (44%) were known HIV positive. Overall, records showed 57/639 (8.9%) were HIV positive of whom 39/57 (68.4%) had previously-diagnosed infection and 18/57 (31.6%) newly-diagnosed infection. Of the 428 participants who self-reported a result, 366 (85.5%) reported by SMS. CONCLUSIONS: HIVST can improve HIV testing uptake and linkage to care. SMS is acceptable for reporting HIVST results but negative self-reports by participants may be unreliable. Use of HIVST by individuals on ART is frequent despite recommendations to the contrary and its implications need further consideration.

Stock-outs of antiretroviral and tuberculosis medicines in South Africa: A national cross-sectional survey.

BACKGROUND: HIV and TB programs have rapidly scaled-up over the past decade in Sub-Saharan Africa and uninterrupted supplies of those medicines are critical to their success. However, estimates of stock-outs are largely unknown. This survey aimed to estimate the extent of stock-outs of antiretroviral and TB medicines in public health facilities across South Africa, which has the world's largest antiretroviral treatment (ART) program and a rising multidrug-resistant TB epidemic. METHODS: We conducted a cross-sectional telephonic survey (October-December 2015) of public health facilities. Facilities were asked about the prevalence of stock-outs on the day of the survey and in the preceding three months, their duration and impact. RESULTS: Nationwide, of 3547 eligible health facilities, 79% (2804) could be reached telephonically. 88% (2463) participated and 4% (93) were excluded as they did not provide ART or TB treatment. Of the 2370 included facilities, 20% (485) reported a stock-out of at least 1 ARV and/or TB-related medicine on the day of contact and 36% (864) during the three months prior to contact, ranging from 74% (163/220) of health facilities in Mpumalanga to 12% (32/261) in the Western Cape province. These 864 facilities reported 1475 individual stock-outs, with one to fourteen different medicines out of stock per facility. Information on impact was provided in 98% (1449/1475) of stock-outs: 25% (366) resulted in a high impact outcome, where patients left the facility without medicine or were provided with an incomplete regimen. Of the 757 stock-outs that were resolved 70% (527) lasted longer than one month. INTERPRETATION: There was a high prevalence of stock-outs nationwide. Large interprovincial differences in stock-out occurrence, duration, and impact suggest differences in provincial ability to prevent, mitigate and cope within the same framework. End-user monitoring of the supply chain by patients and civil society has the potential to increase transparency and complement public sector monitoring systems.

Removal of user fees and system strengthening improves access to maternity care, reducing neonatal mortality in a district hospital in Lesotho.

OBJECTIVE: Lesotho has one of the highest maternal mortality rates in the world. While at primary health care (PHC) level maternity care is free, at hospital level co-payments are required from patients. We describe service utilisation and delivery outcomes before and after removal of user fees and quality of delivery care, and associated costs, at St Joseph's Hospital (SJH) in Roma, Lesotho. METHODS: We compared utilisation of delivery services, stillbirths and maternal and neonatal mortality for the periods before (1 July 2012 to 31 December 2013) and after (1 January 2014 to 30 June 2015) user fee removal through a retrospective chart review and estimated additional costs attributed to user fee removal from provider (hospital) and patient perspectives. RESULTS: Of 4715 deliveries 3855 were at SJH and 860 at PHC centres. Of women delivering at SJH 684 (18.5%) were ≤19 years and 894 (23.6%) were HIV positive. After user fee removal hospital deliveries increased by 49% - from 1547 to 2308 - and neonatal mortality decreased from 4.8 to 1.3 per 1000 live births (P = 0.033). Extrapolating costs to the entire country, 1 USD per capita per year would allow user fee removal at hospital level, the provision of free transport to/from and accommodation at hospital. CONCLUSION: Removing user fees for hospital delivery care in Lesotho is feasible and affordable, and has the potential to improve maternal and neonatal outcomes by removing financial barriers to skilled birth attendants and increasing coverage of institutional deliveries.

The impact of lay counselors on HIV testing rates: quasi-experimental evidence from lay counselor redeployment in KwaZulu-Natal, South Africa.

OBJECTIVES: This study aimed to determine the causal effect of the number of lay counselors removed from a primary care clinic in rural South Africa on the number of clinic-based HIV tests performed. DESIGN: Fixed-effects panel analysis. METHODS: We collected monthly data on the number of lay counselors employed and HIV tests performed at nine primary care clinics in rural KwaZulu-Natal from January 2014 to December 2015. Using clinic-level and month-level fixed-effects regressions, we exploited the fact that lay counselors were removed from clinics at two quasi-random time points by a redeployment policy. RESULTS: A total of 24 526 HIV tests were conducted over the study period. Twenty-one of 27 lay counselors were removed across the nine clinics in the two redeployment waves. A 10% reduction in the number of lay counselors at a clinic was associated with a 4.9% [95% confidence interval (CI) 2.8-7.0, P < 0.001] decrease in the number of HIV tests performed. In absolute terms, losing one lay counselor from a clinic was associated with a mean of 29.7 (95% CI 21.2-38.2, P < 0.001) fewer HIV tests carried out at the clinic per month. CONCLUSION: This study provides some evidence that lay counselors play an important role in the HIV response in rural South Africa. More broadly, this analysis adds some empirical support to plans to increase the involvement of lay health workers in the HIV response.

Delamanid for rifampicin-resistant tuberculosis: a retrospective study from South Africa.

Experience with delamanid (Dlm) is limited, particularly among HIV-positive individuals. We describe early efficacy and safety data from a programmatic setting in South Africa.This was a retrospective cohort study of patients receiving Dlm-containing treatment regimens between November 2015 and August 2017. We report 12-month interim outcomes, sputum culture conversion (SCC) by months 2 and 6, serious adverse events (SAEs) and QT intervals corrected using the Frederica formula (QTcF).Overall, 103 patients were initiated on Dlm; 79 (77%) were HIV positive. The main indication for Dlm was intolerance to second-line anti-tuberculosis (TB) drugs (n=58, 56%). There were 12 months of follow-up for 46 patients; 28 (61%) had a favourable outcome (cure, treatment completion or culture negativity). Positive cultures were found for 57 patients at Dlm initiation; 16 out of 31 (52%) had SCC within 2 months and 25 out of 31 (81%) within 6 months. There were 67 SAEs reported in 29 patients (28%). There were four instances of QTcF prolongation >500 ms in two patients (2%), leading to permanent discontinuation in one case; however, no cardiac arrhythmias occurred.This large cohort of difficult-to-treat patients receiving Dlm for rifampicin-resistant TB treatment in a programmatic setting with high HIV prevalence had favourable early treatment response and tolerated treatment well. Dlm should remain available, particularly for those who cannot be treated with conventional regimens or with limited treatment options.

Cryptococcal antigen screening by lay cadres using a rapid test at the point of care: A feasibility study in rural Lesotho.

INTRODUCTION: Cryptococcal meningitis is one of the leading causes of death among people with HIV in Africa, primarily due to delayed presentation, poor availability and high cost of treatment. Routine cryptococcal antigen (CrAg) screening of patients with a CD4 count less than 100 cells/mm3, followed by pre-emptive therapy if positive, might reduce mortality in high prevalence settings. Using the cryptococcal antigen (CrAg) lateral flow assay (LFA), screening is possible at the point of care (POC). However, critical shortages of health staff may limit adoption. This study investigates the feasibility of lay counsellors conducting CrAg LFA screening in rural primary care clinics in Lesotho. METHODS: From May 2014 to June 2015, individuals who tested positive for HIV were tested for CD4 count and those with CD4 <100 cells/mm3 were screened with CrAg LFA. All tests were performed by lay counsellors. CrAg-positive asymptomatic patients received fluconazole, while symptomatic patients were referred to hospital. Lay counsellors were trained and supervised by a laboratory technician and counsellor activity supervisor. Additionally, nurses and doctors were trained on CrAg screening and appropriate treatment. RESULTS: During the study period, 1,388 people were newly diagnosed with HIV, of whom 129 (9%) presented with a CD4 count <100 cells/mm3. Of these, 128 (99%) were screened with CrAg LFA and 14/128 (11%) tested positive. Twelve of the 14 (86%) were asymptomatic, and received outpatient fluconazole. All commenced ART with a median time to initiation of 15.5 days [IQR: 14-22]. Of the asymptomatic patients, nine (75%) remained asymptomatic after a median time of 5 months [IQR; 3-6] of follow up. One (8%) became co-infected with tuberculosis and died and two were transferred out. The two patients with symptomatic cryptococcal meningitis (CM) were referred to hospital, where they later died. CONCLUSIONS: CrAg LFA screening by lay counsellors followed by pre-emptive fluconazole treatment for asymptomatic cases, or referral to hospital for symptomatic cases, proved feasible. However, regular follow-up to ensure proper management of cryptococcal disease was needed. These early results support the wider use of CrAg LFA screening in remote primary care settings where upper cadres of healthcare staff may be in short supply.

DOT or SAT for Rifampicin-resistant tuberculosis? A non-randomized comparison in a high HIV-prevalence setting.

BACKGROUND: Daily directly-observed therapy (DOT) is recommended for rifampicin-resistant tuberculosis (RR-TB) patients throughout treatment. We assessed the impact of self-administered treatment (SAT) in a South African township with high rates of RR-TB and HIV. METHODS: Community-supported SAT for patients who completed the intensive phase was piloted in five primary care clinics in Khayelitsha. We compared final treatment outcomes among RR-TB patients initiating treatment before (standard-of-care (SOC)-cohort, January 2010-July 2013) and after the implementation of the pilot (SAT-cohort, January 2012-December 2014). All patients with outcomes before January 1, 2017 were considered in the analysis of outcomes. RESULTS: One-hundred-eighteen patients in the SOC-cohort and 174 patients in the SAT-cohort had final RR-TB treatment outcomes; 70% and 73% were HIV-co-infected, respectively. The proportion of patients with a final outcome of loss to follow-up (LTFU) did not differ whether treated in the SOC (25/118, 21.2%) or SAT-cohort (31/174, 17.8%) (P = 0.47). There were no significant differences in the time to 24-month LTFU among HIV-infected and uninfected patients (HR 0.90, 95% CI: 0.51-1.6, P = 0.71), or among patients enrolled in the SOC-cohort versus the SAT-cohort (HR 0.83, 95% CI: 0.49-1.4, P = 0.50) who received at least 6-months of RR-TB treatment. CONCLUSION: The introduction of SAT during the continuation phase of RR-TB treatment does not adversely affect final RR-TB treatment outcomes in a high TB and HIV-burden setting. This differentiated, patient-centred model of care could be considered in RR-TB programmes to decrease the burden of DOT on patients and health facilities.

One-year evaluation of the impact of an emergency obstetric and neonatal care training program in Western Kenya.

OBJECTIVE: To determine the impact of introducing an emergency obstetric and neonatal care training program on maternal and perinatal morbidity and mortality at Moi Teaching and Referral Hospital, Eldoret, Kenya. METHODS: A prospective chart review was conducted of all deliveries during the 3-month period (November 2009 to January 2010) before the introduction of the Advances in Labor and Risk Management International Program (AIP), and in the 3-month period (August-November 2011) 1 year after the introduction of the AIP. All women who were admitted and delivered after 28 weeks of pregnancy were included. The primary outcome was the direct obstetric case fatality rate. RESULTS: A total of 1741 deliveries occurred during the baseline period and 1812 in the postintervention period. Only one mother died in each period. However, postpartum hemorrhage rates decreased, affecting 59 (3.5%) of 1669 patients before implementation and 40 (2.3%) of 1751 afterwards (P=0.029). The number of patients who received oxytocin increased from 829 (47.6%) to 1669 (92.1%; P<0.001). Additionally, the number of neonates with 5-minute Apgar scores of less than 5 reduced from 133 (7.7%) of 1717 to 95 (5.4%) of 1745 (P=0.006). CONCLUSION: The introduction of the AIP improved maternal outcomes. There were significant differences related to use of oxytocin and postpartum hemorrhage.

Are plasma biomarkers of immune activation predictive of HIV progression: a longitudinal comparison and analyses in HIV-1 and HIV-2 infections?

BACKGROUND: Chronic immune activation is a hallmark of HIV infection and has been associated with disease progression. Assessment of soluble biomarkers indicating immune activation provide clues into pathogenesis and hold promise for the development of point-of-care monitoring of HIV in resource-poor-settings. Their evaluation in cohort resources is therefore needed to further their development and use in HIV research. METHODOLOGY/PRINCIPAL FINDINGS: Longitudinal evaluation of ßeta-2 microglobulin (ß-2 m), neopterin and suPAR soluble urokinase-type plasminogen activator receptor (suPAR) was performed with archived plasma samples to predict disease progression and provided the first direct comparison of levels in HIV-1 and HIV-2 infections. At least 2095 samples from 137 HIV-1 and 198 HIV-2 subjects with starting CD4% of ≥ 28 and median follow up of 4 years were analysed. All biomarkers were correlated negatively to CD4% and positively to viral load and to each other. Analyses in subjects living for ≥ 5 years revealed increases in median ß-2 m and neopterin and decreases in CD4% over this period and the odds of death within 5 years were positively associated with baseline levels of ß-2 m and neopterin. ROC analyses strengthened the evidence of elevation of biomarkers in patients approaching death in both HIV-1 and HIV-2 infections. Regression models showed that rates of biomarker fold change accelerated from 6-8 years before death with no significant differences between biomarker levels in HIV-1 and HIV-2 at equal time points prior to death.An 'immune activation index' analysis indicative of biomarker levels at equivalent viral loads also showed no differences between the two infections. CONCLUSIONS/SIGNIFICANCE: Our results suggest that ß-2 m and neopterin are useful tools for disease monitoring in both HIV-1 and HIV-2 infections, whereas sUPAR performed less well. Levels of immune activation per amount of virus were comparable in HIV-1 and HIV-2 infected subjects.